112 Chapter 5
The production of NADH and FADH 2 by each “turn”
of the citric acid cycle is far more significant, in terms of
energy production, than the single GTP (converted to ATP)
produced directly by the cycle. This is because NADH
and FADH 2 eventually donate their electrons to an energy-
transferring process that results in the formation of a large
number of ATP.
Electron Transport and Oxidative
Phosphorylation
Built into the foldings, or cristae, of the inner mitochondrial
membrane are a series of molecules that serve as an electron-
transport system during aerobic respiration. This electron-
transport chain of molecules consists of a protein containing
flavin mononucleotide (abbreviated FMN and derived from
the vitamin riboflavin), coenzyme Q, and a group of iron-
containing pigments called cytochromes. The last of these
cytochromes is cytochrome a 3 , which donates electrons to
oxygen in the final oxidation-reduction reaction (as will be
described shortly). These molecules of the electron-transport
system are fixed in position within the inner mitochondrial
membrane in such a way that they can pick up electrons from
NADH and FADH 2 and transport them in a definite sequence
and direction.
In aerobic respiration, NADH and FADH 2 become oxi-
dized by transferring their pairs of electrons to the electron-
transport system of the cristae. It should be noted that the
protons (H^1 ) are not transported together with the electrons;
their fate will be described a little later. The oxidized forms
of NAD and FAD are thus regenerated and can continue to
“shuttle” electrons from the citric acid cycle to the electron-
transport chain. The first molecule of the electron-transport
chain becomes reduced when it accepts the electron pair
from NADH. When the cytochromes receive a pair of elec-
trons, 2 ferric ions (Fe^3 1 ) become reduced to 2 ferrous ions
(Fe^2 1 ).
The electron-transport chain thus acts as an oxidizing
agent for NAD and FAD. Each element in the chain, however,
also functions as a reducing agent; one reduced cytochrome
transfers its electron pair to the next cytochrome in the chain
( fig. 5.8 ). In this way, the iron ions in each cytochrome alter-
nately become reduced (from Fe^3 1 to Fe^2 1 ) and oxidized (from
Fe^2 1 to Fe^3 1 ). This is an exergonic process, and the energy
derived is used to phosphorylate ADP to ATP. The production
of ATP through the coupling of the electron-transport system
with the phosphorylation of ADP is appropriately termed
oxidative phosphorylation.
The coupling is not 100% efficient between the energy
released by electron transport (the “oxidative” part of oxi-
dative phosphorylation) and the energy incorporated into the
chemical bonds of ATP (the “phosphorylation” part of the
term). This difference in energy escapes the body as heat.
Metabolic heat production is needed to maintain our internal
body temperature.
Coenzyme A acts only as a transporter of acetic acid from one
enzyme to another (similar to the transport of hydrogen by
NAD). The formation of citric acid begins a cyclic metabolic
pathway known as the citric acid cycle, or TCA cycle (for tri-
carboxylic acid; citric acid has three carboxylic acid groups). It
is often also called the Krebs cycle, after its principal discov-
erer, Sir Hans Krebs. A simplified illustration of this pathway
is shown in figure 5.6.
Through a series of reactions involving the elimination of
2 carbons and 4 oxygens (as 2 CO 2 molecules) and the removal
of hydrogens, citric acid is eventually converted to oxaloacetic
acid, which completes the cyclic metabolic pathway ( fig. 5.7 ).
In this process, these events occur:
1. One guanosine triphosphate (GTP) is produced (step 5 of
fig. 5.7 ), which donates a phosphate group to ADP to pro-
duce one ATP.
2. Three molecules of NAD are reduced to NADH (steps 4,
5, and 8 of fig. 5.7 ).
3. One molecule of FAD is reduced to FADH 2 (step 6).
Figure 5.6 A simplified diagram of the citric acid
cycle. This diagram shows how the original four-carbon-
long oxaloacetic acid is regenerated at the end of the cyclic
pathway. Only the numbers of carbon atoms in the citric acid
cycle intermediates are shown; the numbers of hydrogens and
oxygens are not accounted for in this simplified scheme.
CYTOPLASM
C 3
C 2
C 4
C 5
C 6
Pyruvic acid
Citric acid
3 NADH + H+
1 FADH 2
1 ATP
Acetyl CoA
NAD
NADH + H+
Mitochondrial matrix CoA
Glycolysis
Oxaloacetic acid
CO 2
CO 2
CO 2
훂-Ketoglutaric acid
Citric acid
cycle